tbuckley/cabot-search huggingface dataset:
Outcomes among patients with pancreatic malignancy on long-term anticoagulation hospitalized for acute pulmonary embolism: A nationwide analysis.
Authors: Arshi Syal, Yajur Arya, Bruce Adrian Casipit, Claudia Dourado
Journal: Journal of Clinical Oncology (2023)

e16266 Background: Pancreatic cancer is known to have an increased risk of thromboembolic events. Acute pulmonary embolism further complicates the clinical picture and confers a poor prognosis in this population. Data regarding prophylactic anticoagulation in patients with pancreatic malignancy is lacking, although there is evidence that prophylaxis does reduce incidence of venous thromboembolism in pancreatic malignancy. Whether this benefit equates to improved clinical outcomes needs further clarification. Methods: We utilized the 2018-2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study. We identified patients who have pancreatic malignancy and acute pulmonary embolism using appropriate ICD-10 CM codes. We stratified patients based on the presence or absence of long-term anticoagulation. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of &lt;0.05 was considered statistically significant. The aim of this study is to investigate the outcomes among patients with pancreatic malignancy hospitalized for acute pulmonary embolism looking primarily at the in-hospital mortality, hospital length of stay (LOS) as well as total hospital charges. Results: We identified a total of 160,000 hospitalized patients with acute pulmonary embolism, of which 0.6% (1,120/160,000) had malignant neoplasm of the pancreas and 20.09% (225/1120) are on long-term anticoagulation. The overall in-hospital mortality among those with pancreatic malignancy hospitalized for acute PE was 5.91% (66/1,120). Among those who are on long-term anticoagulation, the overall in-hospital mortality rate was lower at 4.44% (10/225), however, it was not significantly different from those who are not on anticoagulation 6.29% (14/225) (p value=0.64). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, the use of long-term anticoagulation among hospitalized acute PE patients with history of pancreatic malignancy did not significantly decrease risk for in-hospital mortality (adjusted OR 0.37; 95% confidence interval [CI], 0.09-1.57; p=0.18), hospital LOS (adjusted OR 0.80; 95% confidence interval [CI], 0.63-10.26; p=0.86) or total hospital charges (p=0.32). Conclusions: Our analysis showed that among patients with pancreatic malignancy hospitalized for acute pulmonary embolism, the use of prior long-term anticoagulation did not significantly decrease the risk for in-hospital mortality, hospital LOS as well as total hospital charges. Prospective studies with control of possible confounders are warranted to further clarify the use of prophylactic anticoagulation in pancreatic malignancy and its impact on outcomes.
Real-world efficacy and safety of donafenib-based therapies in patients with unresectable hepatocellular carcinoma: A retrospective study.
Authors: Changzhen Shang, Xuan Luo, Jinyi Zhong, Jianlong Zhang, Huilong Li, Wenliang Tan, Zhang Lei, Yajin Chen
Journal: Journal of Clinical Oncology (2023)

e16169 Background: According to the results of phase III ZGDH3 study, donafenib has significantly improved overall survival (OS) versus sorafenib in first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). The present study aimed to evaluate the efficacy and safety of donafenib-based therapies in patients with uHCC regardless of first- or later-line systemic therapy. Methods: This single-center retrospective study involved 30 patients with histopathologically/cytologically or clinically confirmed uHCC at Sun Yat-sen Memorial Hospital, Sun Yat-sen University between August 2021 and February 2022. Eligible patients underwent donafenib-based therapies until disease progression, death, or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included OS, objective response rate (ORR), disease control rate (DCR), and safety. Tumor response was determined according to the RECIST v1.1 and modified (m)RECIST. Results: Of these eligible 30 patients, the median age was 55 years (range, 27–73), 93% were male, 93% with HBV and 63% were BCLC C. Donafenib was commonly used as a monotherapy (17%) or in combination with immune checkpoint inhibitors (ICIs), transarterial therapy, both, or other treatments. Twenty (67%) patients underwent donafenib-based therapies as a first-line treatment, of which 15 (75%) underwent a triple combination of donafenib, ICIs, and transarterial therapy. By the cutoff date of January 2023, the median PFS and OS were not yet reached; the 6-month PFS and OS rates were 70.0% and 90.0%, respectively, and the 12-month PFS and OS rates were 66.5% and 86.5%, respectively. The ORR and DCR for all patients were 43.3% and 73.3%, respectively, based on both RECIST v1.1 (CR 4 [13.3%], PR 9 [30.0%], SD 9 [30.0%]) and mRECIST (CR 5 [16.7%], PR 8 [26.7%], SD 9 [30.0%]). Among the 20 patients who underwent donafenib-based first-line systemic therapy, the ORRs according to RECIST v1.1 and mRECIST were both 55.0%, and higher ORRs (73.3% per RECIST v1.1 and mRECIST) were observed in 15 patients who underwent donafenib, ICIs, and transarterial therapy. Overall, 15 (50.0%) patients had more than one treatment-related adverse event (TRAEs) and the most common AEs were hand-foot skin reaction (26.7%), rash (10.0%), and gingival bleeding (10.0%). Grade 3 AEs occurred in 16.7% of patients. No TRAE led to death in the study. Conclusions: This study indicated that donafenib-based therapies, particularly donafenib in combination with ICIs plus transarterial therapy, show promising antitumor activity in patients with uHCC, and no new safety signals were observed in real-world settings. Clinical trial information: ChiCTR2200063822 .
Comparison of peripheral blood markers in predicting the occurrence of immune-related adverse events in patients with metastatic genitourinary cancer treated with cabozantinib + nivolumab +/- ipilimumab.
Authors: Giovanni Maria Iannantuono, Elias Chandran, Nicholas I. Simon, Lisa Ley, Lisa M. Cordes, Tzu-fang Wang, Daniel da Motta Girardi, Sandeep Gurram, Vladimir Valera, Heather Chalfin, Howard L. Parnes, Rosa Nadal, Scot Anthony Niglio, Salah Boudjadi, Abdul Rouf Banday, Andre Rashad Kydd, Seth M. Steinberg, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2023)

e16506 Background: Peripheral blood markers (PBM) have been demonstrated to be prognostic and/or predictive for cancer patients (pts) treated with immune checkpoint inhibitors (ICI). Initial evidence has shown their potential role in predicting the occurrence of immune-related adverse events (IrAE) in pts treated with single-agent ICI. We explored the potential role of different PBM in predicting IrAE in metastatic genitourinary cancer (mGU) pts treated with an ICI-based combination. Methods: We retrospectively evaluated 60 mGU pts treated with Cabozantinib + Nivolumab +/- Ipilimumab (CaboNivo +/- Ipi) in a phase I study at the National Cancer Institute. We retrieved their demographics, the occurrence of IrAE, and the baseline values of different PBM (neutrophil/lymphocyte ratio [NLR], neutrophil/eosinophil ratio [NER], lymphocyte/monocyte ratio [LMR], monocyte/lymphocyte ratio [MLR], platelet/lymphocyte ratio [PLR], systemic immune-inflammation index [SII] [N/L*P], and HALP score [albumin*hemoglobin*L/P]). We evaluated PBM based on the presence or absence of IrAE using the Wilcoxon rank sum test followed by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analyses were used to investigate an optimal cut-off for PBM suitable for prediction. Results: The median age of pts was 58.5 years (interquartile range [IQR] 46 - 67), and 13 (21.7%) were female. Twenty (33.3%) pts developed at least one IrAE. Baseline median values of PMB are summarized in the Table. A multivariable logistic regression model showed after backward elimination that only NER had the potential to predict IrAE (p = 0.033; Odds Ratio = 0.989 per unit [95% Confidence Interval 0.979 - 0.999]) and thus, we further investigated the predictive potential of NER for the development of IrAE following CaboNivo +/- Ipi. The ROC curve suggested that an optimal cut-off value for NER was 30.647 (area under the ROC = 0.6351). Accordingly, we classified pts with high NER ( &gt; 30.647) as not having IrAE vs low NER (≤ 30.647) as having IrAE. Using this classification, 24/37 (64.9%) of those without (w/o) IrAE and 14/20 (80%) of those with an IrAE could simultaneously be correctly predicted by NER alone. Conclusions: A baseline low NER value was an independent factor associated with a higher probability of developing IrAE in mGU pts treated with CaboNivo +/- Ipi. Prospective validation on a larger cohort of pts is needed. [Table: see text]
Lu-PSMA-617 in combination with third-line therapy for castration-resistant prostate cancer: A systemic review and meta-analysis.
Authors: Usman Ali Akbar, Fatima Ali, Sindhu Vikash, Saad Khalid, Sabeeh Farooqui, Aleena Aman, Shaheryar Qazi, - Muhibullah, Abdul Qadeer, Mohammad Ebad Ur Rehman, Rameesha Zubair, Muhammad Aizaz Ashraf, Muhammad Asad Shabbir, Muhammad Ihsan Ahmed, Alina Khalid
Journal: Journal of Clinical Oncology (2023)

e17051 Background: Prostate cancer is the second most common cancer and the sixth leading cause of cancer death among men worldwide. Lu-177 viptriplet, also known as lutetium-177-PSMA-617, is a highly targeted form of radioligand therapy that aims to shrink prostate cancer tumors and slow their progression. It is also recommended as a treatment option by the American Society of Clinical Oncology (ASCO) for patients with prostate-specific membrane antigen (PSMA) positive PET/CT-positive castration resistant prostate cancer (CRPC) who have progressed on at least one prior line of androgen receptor pathway inhibitors (ARPI) and at least one prior line of chemotherapy. However, the evidence on its effectiveness with third-line chemotherapy is scarce. We aim to evaluate the efficacy of Luma-PSMA plus third-line chemotherapy in CRPC. Methods: We conducted a comprehensive literature search in PubMed, PMC, Scopus, and Embase using relevant keywords to identify articles related to Luma-PSMA and third line chemotherapy for prostate cancer from inception to Jan 30, 2023. Three independent reviewers screened the articles for eligibility and extracted data on outcomes such as overall survival (OS), PSA decline &gt; 50%, and partial remission. We used Raveman 5 software to perform a statistical analysis and calculated the odds ratio with a 95% confidence interval for each outcome. Results: A total of 11 studies were included in our analysis with 787 patients. Pooled analysis of studies demonstrated an overall survival after Lu-PSMA-617 therapy plus third line chemotherapy as compared to standalone chemotherapy in castration resistant prostate cancer to be 13.15 months (95% CI = 10.66 – 15.65, P = &lt; 0.001, I 2 = 69.93%). Pooled prevalence of prostate specific antigen (PSA) decline &gt; 50% was determined to be 49.5% (95% CI = 44.2 – 54.7, P = 0.162 I 2 = 33.27%) and partial remission was observed in 39.7% patients (95% CI = 28.5 – 50.9, P = 0.952 I 2 = 0%). Conclusions: Our meta-analysis suggests that Lu-PSMA-617 therapy plus third-line chemotherapy may improve overall survival and PSA response in patients with CRPC compared to chemotherapy alone. However, the quality of evidence is limited by heterogeneity and risk of bias. More high-quality randomized trials are needed to confirm the efficacy and safety of this combination therapy. [Table: see text]
Comparative efficacy of zanubrutinib (ZANU) versus rituximab (RTX) in relapsed marginal zone lymphoma (MZL): Matching-adjusted indirect comparison (MAIC).
Authors: Catherine Thieblemont, Kaijun Wang, Sam Keeping, Ina Zhang, Keri Yang, Boxiong Tang, Leyla Mohseninejad
Journal: Journal of Clinical Oncology (2023)

e19526 Background: ZANU is a Bruton tyrosine kinase inhibitor that has been evaluated for relapsed/refractory MZL in two phase 2, single-arm (MAGNOLIA, n=66, NCT03846427; BGB-3111-AU-003, n=20, NCT02343120). At 28 and 35 months of study follow-up in MAGNOLIA and BGB-3111-AU-003, respectively, median progression-free survival (PFS) and overall survival (OS) were not reached. Here, we conducted an unanchored MAIC to estimate relative treatment effects of ZANU vs RTX, a commonly used treatment for patients with relapsed MZL. Note the comparison was restricted to the relapsed population because RTX refractory patients would not be retreated with RTX. Methods: The MAIC was performed using pooled individual patient-level data from MAGNOLIA and BGB-3111-AU-003. Study level-data of RTX in relapsed patients were used from CHRONOS-3 (Özcan et al., Ann Oncol 2021) which was identified as the most suitable comparator study via a systematic literature review. A logistic propensity score model was used to estimate weights for patients in ZANU trials such that their weighted mean baseline characteristics matched those of CHRONOS-3. The following characteristics were identified as key prognostic factors and included in the base case propensity score model: prior lines of therapy, MZL subtype, relapse after prior therapy, and age. Sensitivity analyses incorporating additional characteristics were not possible owing to a lack of reporting from CHRONOS-3, but the impact of each covariate in the base model was explored via a leave-one-out analysis. Comparisons were conducted for OS, PFS, and objective response rate (ORR) by independent review committee using weighted statistical models, with relative treatment effects presented as hazard ratios (HRs), odds ratios (ORs), and 95% CIs. Results: After applying weights estimated from the base case propensity score model, the effective sample size (ESS) for ZANU was 39. ZANU reduced the risk of progression (HR 0.29; 95% CI 0.13–0.65) and had a higher probability of response (OR 5.09; 95% CI: 1.84–14.08) when compared with RTX (Table). OS was comparable for ZANU and RTX, which is consistent with the survival expectancy for indolent lymphomas. The leave-one-out analysis showed that removing any of the characteristics from the propensity score model yielded comparable results. Conclusions: MAIC results suggest ZANU is associated with improved PFS and ORR compared with RTX in relapsed MZL. [Table: see text]
Updated results of anlotinib combined with TQB2450 (PD-L1 blockade) as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, multicenter, open-label phase Ⅱ clinical trial.
Authors: Zhiye Zhang, Xiangrui Meng, Xiuli Yang, Yong-Gui Hong, Jin Xia, Yunfang Chen, Tao Wu, Zheng-Zheng Shan, Qingxia Fan, Feng Wang
Journal: Journal of Clinical Oncology (2023)

4041 Background: PD-1 blockades combined with chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC recently. However, the safety profile of conventional chemotherapy was still disappointing. Therefore, the chemotherapy-free regimen might be a promising strategy. As a novel multitarget TKI mainly targeting VEGFR1-3, anlotinib was a potential first-line combination therapy and second-line monotherapy for patients with ESCC in China. TQB2450 was a novel PD-L1 blockade developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Nanjing, China). Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with TQB2450 as first-line therapy in advanced ESCC. The preliminary results were reported in 2023 ASCO-GI Symposium (Abs 377) and the update results were reported here. Methods: Patients with previously untreated metastatic or locally advanced ESCC, whose age was between 18 and 75 years, with ECOG PS of 0 or 1 and life expectancy of &gt; 3 months were eligible as the inclusion criteria. Eligible patients were administered with anlotinib (12mg, po, d1~14, q3w) plus TQB2450 (1200mg, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 and iRECIST using CT scans every 2 cycles for the first 6 cycles, and every 3 cycles thereafter. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 46. The primary endpoint was ORR. Secondary endpoints included safety, PFS, DCR, DoR and OS. Results: From Mar 2022 to Sep 2022, a total of 46 patients were enrolled. At the data cut-off date (Dec, 2022), there were 1 CR (2.2%), 27 PR (58.7%), 14 SD (30.4%) and 4 NE (8.7%). Therefore, the preliminary ORR was 60.9% (95%CI: 45.4%~74.9%), DCR was 91.3% (95%CI: 79.2%~97.6%). The median PFS of the 46 pts was not yet available. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-related adverse events in 46 patients with the incidence &gt; 10% were hypertension (28%), hypothyroidism (20%), leukocytosis (20%), hyperthyroidism (17%), anemia (15%), fatigue (15%), neutrophil count decreased (11%), constipation (11%), sinus bradycardia (11%) and hand-foot syndrome (11%). The common grade ≥3 treatment-related adverse events were hypertension (4%), hand-foot syndrome (2%), hyponatremia (2%), platelet count decreased (2%) and lymphocyte count decreased (2%). Conclusions: Preliminary results suggested that anlotinib combined with TQB2450 as first-line therapy in advanced ESCC exhibited encouraging efficacy and manageable adverse events. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: NCT05038813 .
Differences in outcomes of patients with advanced neuroendocrine tumors treated with chemotherapy versus targeted agents.
Authors: Jesica Freeman, Jennifer Stacey
Journal: Journal of Clinical Oncology (2023)

e16303 Background: Pancreas NETs are uncommon and very rare cancer accounting for around 7% of the pancreatic cancer sub patient population, 4,200 patients in the US diagnoses yearly of all cancers in the pancreas. There are very few treatment options available for Metastatic Pancreatic Neuroendocrine Tumor patients. The survival rate depends on a variety of factors, including whether the tumor can be removed using surgery and if the cancer has spread to other parts of the body. The 5-year survival rate non-metastatic pancreas NETs is 93% while metastatic pancreas NETs is 24%. Therefore, this study compares the 5-year overall survival rate of metastatic pancreatic NETs ineligible for surgery who have received chemotherapy alone versus who have received targeted therapy. Methods: Patient cohorts were generated in an electronic medical records (EMR) TriNetX Research Network of 89M patient lives. Patients were identified as either receiving a targeted therapy or patients who were targeted therapy naïve receiving chemotherapy. Both cohorts had a diagnosis of pancreatic NETs (ICD-10 C25.4), at least one documentation of a related metastasis, and no history of any pancreatic surgery. The 5 year overall survival (OS) from first exposure to either targeted therapy or chemotherapy was analyzed using measures of association and survival analysis conducted via Kaplan-Meier estimator. Cohort comparisons were with propensity score matching (PSM) to control for demographic, comorbidity, medication, and diagnostic procedure confounders. Results: After matching, each cohort accounted for 389 patients (43% female, mean age at index 62 +/- 13 SD). There was a significant 5-year mortality risk difference (11.054%, p = 0.0020) between the chemotherapy only cohort (215 patients, 55.27%) vs. the targeted therapy cohort (172 patients, 44.216%) after adjusting for potential confounding factors. Additionally, the 5-year OS rate was 24.951% in the chemotherapy only cohort and 37.222% in the targeted therapy cohort. The difference in survival between the groups was statistically significant (log-rank p = 0.0001). Conclusions: In these cohorts of patients with metastatic pancreas NETs without surgical treatment, we found that targeted therapy was associated with a significant improvement in 5-year overall survival compared to standard chemotherapy alone. Our results suggest that targeted therapy should be considered as a first line treatment option for this severe patient population.
The activity and safety of anlotinib for patients with recurrent malignant glioma: A single-center, retrospective study.
Authors: Xudong Sun, Min-Jie Li, Xue-ying Zhang, Yue-feng Shen
Journal: Journal of Clinical Oncology (2023)

e14032 Background: Anlotinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) 1/2/3, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR) 1/2/3/4, c-Kit, and Ret. We report results from this retrospective study to determine the efficacy and tolerability of Anlotinib as a treatment for recurrent malignant glioma (rMG). Methods: A total of 26 eligible patients who relapsed from the standard chemoradiotherapy regimen (TMZ and radiotherapy) after surgery because of tumor located in the eloquent brain areas were enrolled in this study between May 2020 and August 2022. Patients were subjected to a concurrent treatment of Anlotinib (12mg qd) until disease progression or intolerable toxicity. Efficacy was evaluated using Response Assessment in Neuro-Oncology criteria for high-grade glioma. Safety was assessed using NCI-CTCAE 5.0. Survival was estimated with the Kaplan-Meier curve and log-rank test. Results: In total, 26 (11 male, 15 female) patients with recurrent malignant glioma were enrolled. The disease control rate was 84.6% (95%CI 36.9%-76.7%) and the objective response rate was 57.7%(95%CI 65.1%-95.6%). The median progress-free survival (PFS) for all patients was 9.0 months (95%CI 2.88-15.19). The most common treatment-related adverse events were hand-foot syndrome (38.5%), Weakness (38.5%), hypertension 30.8%) and there were no Grade ≥3 toxicities. Conclusions: The present study showed that anlotinib had a promising efficacy and favorable tolerability in treat rMG. Further randomized controlled clinical studies are needed to confirm the efficacy of Anlotinib for the treatment of rMG.